Hydrochloric Acid → 2-methoxymethyl-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide

HRID 1611946Notes

Reaction equation

HRID 1611946 reaction equation
[CH3:1][OH:2].[H-].[Na+].Cl[CH2:6][C:7]1[CH:8]=[C:9]([CH:30]=[CH:31][N:32]=1)[C:10]([NH:12][C:13]1[O:14][C:15]2[C:21]([CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:20][CH:19]=[C:18]([O:28][CH3:29])[C:16]=2[N:17]=1)=[O:11].Cl>O1CCOCC1.CN(C)C=O>[CH3:1][O:2][CH2:6][C:7]1[CH:8]=[C:9]([CH:30]=[CH:31][N:32]=1)[C:10]([NH:12][C:13]1[O:14][C:15]2[C:21]([CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:20][CH:19]=[C:18]([O:28][CH3:29])[C:16]=2[N:17]=1)=[O:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 24758Sodium hydrideHCID 222522352-chloromethyl-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide

Product 1

HCID 222522502-methoxymethyl-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamideYield 67.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 0.05 ml (1.24 mmol) methanol in 5 ml dioxane and 1 ml N,N-dimethylformamide at room temperature was added 27 mg (0.62 mmol) sodium hydride (55% dispersion in mineral oil), and the mixture heated at 50° C. for 1 hour. 50 mg (0.12 mmol) 2-chloromethyl-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide was then added, and the mixture heated at 50° C. for 20 h. The reaction mixture was then cooled to room temperature and poured onto water. The mixture was acidified with 1 N aq. hydrochloric acid and then extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (dichloromethane) followed by trituration in ether afforded 32 mg (65%) 2-methoxymethyl-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl]-isonicotinamide as a white crystalline solid. ES-MS m/e (%): 398 (M+H+, 100).

Workup

  1. temperaturethe mixture heated at 50° C. for 20 h
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. additionpoured onto water
  4. extractionextracted three times with dichloromethane
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ca947367db434a55b8fc2cbb45723071
Source dataset
uspto-grants-2006_01
Patent number
US06992083B2

Reaction notes

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